Nanoparticle Exposure and Hormetic Dose-Responses: An Update

Abstract

The concept of hormesis, as an adaptive response of biological systems to moderate environmental challenges, has raised considerable nano-toxicological interests in view of the rapid pace of production and application of even more innovative nanomaterials and the expected increasing likelihood of environmental and human exposure to low-dose concentrations. Therefore, the aim of this review is to provide an update of the current knowledge concerning the biphasic dose-responses induced by nanoparticle exposure. The evidence presented confirmed and extended our previous findings, showing that hormesis is a generalized adaptive response which may be further generalized to nanoscale xenobiotic challenges. Nanoparticle physico-chemical properties emerged as possible features affecting biphasic relationships, although the molecular mechanisms underlining such influences remain to be fully understood, especially in experimental settings resembling long-term and low-dose realistic environmental exposure scenarios. Further investigation is necessary to achieve helpful information for a suitable assessment of nanomaterial risks at the low-dose range for both the ecosystem function and the human health.

Keywords: dose–response relationship; hormesis; low doses; nanomaterial.

Figure 1

Main industrial uses and consumer product applications of engineered nanomaterials.

Figure 2

Examples of species-specific biphasic response observed in different bacteria. (A) The respirometry assays showed that NM-300 AgNPs were able to induce a hormetic response only in Gram-positive bacteria (A. agilis and S. koyangensis) (modified by Echavarri-Bravo et al. [18]). (B) The exposure of N. europaea to 35 nm AgNPs affected the transcriptional activity of nitrifying genes (amoA1, amoB2, amoC2, hao2 and sodB) showing a biphasic response. This effect was not evident in other bacteria (P. tutzeri and A. vinelandii) (modified by Yang et al. [19]). * Indicates statistical significance (p < 0.05).

Figure 3

Examples of NP size-dependent biphasic response. (A,B) In E. coli cells, the exposure to Ag-NPs induced a hormetic response regardless of NP size and functionalization (modified by Xiu et al. [16]). (C) Biphasic response of cumulative evapotranspiration was observed in poplars (Populus deltoides × nigra) exposed to carbon- and PEG-coated Ag-NPs of 25 and 10 nm, respectively (modified by Wang et al. [26]). (D) PEG-coated Ag-NPs of 5 and 10 nm affected the root elongation of Arabidopsis thaliana showing a hormetic effect (modified by Wang et al. [26]). (E) Ag-NPs of different size (10 and 100 nm) showed a hormetic cell proliferation response in HepG2 cells (modified by Jiao et al. [13]). (F) Pretreatment of human A549 lung epithelial cells with low doses of Ag-NPs reduced the cytotoxic effect caused by acrolein and/or by exposure to higher doses of the same NPs (modified by Sthijns et al. [12]). * Indicates statistical significance (p < 0.05).

Figure 4

Influence of NP chemical composition on the induction of biphasic response. (A) In E. coli cells, the exposure both to PVP- and PEG-coated Ag-NPs induced a hormetic response (modified by Xiu et al. [16]). (B) In Caco2 cells exposed for 36 h to different concentrations of Ag-NPs and ZnO-NPs, the hormetic response was induced only by Ag-NPs (modified by Kang et al. [14]). (C,D) Cu-NPs at higher concentrations inhibited P. tricornutum growth, while at lower concentrations slightly stimulated growth (modified by Zhou et al. [23]). In the same experimental model, increasing concentrations of CdSe/ZnS-QDs did not induced a hormetic response (modified by Morelli et al. [46]). (E,F) Cu-NPs and Se-NPs induced a different kind of biphasic response related to the grown of Chlorella vulgaris (modified by Mykhaylenko and Zolotareva, [24]). * Indicates statistical significance (p < 0.05).

Figure 5

Influence of experimental conditions on the occurrence of hormesis. (A) The addiction of cysteine in culture media significantly affected the hormetic behavior of Ag-NPs (modified by Guo et al. [17]). (B) Duration of exposure might influence the induction of a biphasic response by Ag-NPs (modified by Razzaq et al. [31]). (C) The hormesis response induced by Ag-NPs in Caenorhabditis elegans is evident following a sub-acute period of exposure, while after 12 days it was no longer observable (modified by Tyne et al. [33]). * Indicates statistical significance (p < 0.05).

Figure 6

Flow diagram of literature search.